Interval to biochemical failure as a biomarker for cause‐specific and overall survival after dose‐escalated external beam radiation therapy for prostate cancer

Abstract

BACKGROUND: After external beam radiation therapy (EBRT) for prostate cancer, a short interval to biochemical failure of <18 months has been proposed as a surrogate for cause‐specific survival. Because EBRT dose influences biochemical failure, the authors investigated the interval to biochemical failure in a cohort of patients treated with dose‐escalated EBRT. METHODS: From 1998 to 2008, 710 patients were treated with EBRT (≥75 grays) ± androgen deprivation therapy (ADT) at the University of Michigan. Biochemical failure was defined using the Phoenix consensus definition (nadir + 2 ng/mL). A short interval to biochemical failure was defined as <18 months after completing radiotherapy and/or ADT. The associations between biochemical failure, the interval to biochemical failure, and clinical factors with cause‐specific survival (CSS) and overall survival (OS) were evaluated. RESULTS: There were 149 biochemical failures (21%), and short interval to biochemical failure accounted for 14% and 40% of biochemical failures in those with intermediate‐risk or high‐risk disease, respectively. Biochemical failure impacted CSS ( P < .0001) but not OS ( P = .36). However, a short interval to biochemical failure predicted decreased CSS ( P < .0001; hazard ratio [HR], 5.6; 95% confidence interval [CI], 2.4‐13.0) and OS ( P < .0001; HR, 4.8; 95% CI, 2.3‐10.3) when compared with a long interval to biochemical failure. The 8‐year OS was 78% without biochemical failure, compared with 87% with a long interval to biochemical failure ( P = .1; HR, 0.7; 95% CI, 0.4‐1.1) and 38% with a short interval to biochemical failure ( P < .0001; HR, 3.7; 95% CI, 2.3‐5.9). On multivariate analysis, a short interval to biochemical failure increased the risk of prostate cancer death ( P < .0001; HR, 18.1; 95% CI, 8.4‐39) and all cause mortality ( P = .0027; HR, 1.5; 95% CI, 1.2‐2.1), whereas a long interval to biochemical failure did not. CONCLUSIONS: The relation between the interval to biochemical failure, CSS, and OS was independently validated in patients treated with dose‐escalated EBRT. Further evaluation of the interval to biochemical failure as a surrogate endpoint is warranted. Cancer 2012. © 2011 American Cancer Society. Because biochemical failure does not predict for overall survival after radiotherapy (RT) in prostate cancer, a short interval to biochemical failure (defined as <18 months after finishing therapy) is tested as a biomarker for both cause‐specific and overall survival. Among 710 patients treated with dose‐escalated RT at the University of Michigan, a short interval to biochemical failure is found to be prognostic of both cause‐specific and overall survival.